Objectives:
The objective was to investigate the influence of two anticholinergic, propiverine and tolterodine on bladder contraction in a standardized in vivo model taking neurogenic innervation into account. In addition, standardized salivary flow measurements enabled the evaluation of hyposalivation, the most predominant anticholinergic side effects. Furthermore, the detrusor electromyogram was evaluated.

Material & Methods:
10 male mini pigs were anaesthesized. The carotic artery was cannulated for blood pressure control and the jugular vein for administration propiverine 0.4 mg/kg b.w and L(+)-tolterodine 0.06 mg/kg b.w. Doses were chosen according to the Defined Daily Dose (DDD). For stimulation-induced salivary flow measurements both lingual nerves were exposed and a cuff electrode was placed around the nerves. The bladder was then exposed and 2 electrodes were implanted under the serosa of the bladder dome to record the bladder EMG and a cystostomy was performed to assess cystometrographic measurements. A bilateral ureterocutaneostomy was performed in order to maintain a constant bladder volume during the trial. The urethra was then ligated to initiate isovolumetric bladder contractions during sacral anterior root stimulation (SARS).

Results:
In all experiments, for each animal reproducible intravesical pressure values (pves) and salivary flow rates were elicted during electrostimulation before administration of the drug. Bladder pressure (tab.): After administration of propiverine, neurostimulation-induced rise in pves dropped about 64% from the initial value. After administration of tolterodine pves declined by about 60%. Salivation: After propiverine salivary flow dropped about 61%. Inhibition of salivary flow under tolterodine was about 54%. Similar results were obtained in bladder EMG recordings. Both propiverine and tolterodine increased the heart rate temporarily at an median of 18%. No change in ECG recordings was noted after administration of the test substances.

Conclusion:
1. The presented model allows comparative in vivo studies of pharmacological effects on bladder function.
2. Both drugs have similar effects on bladder inhibition in mini pigs.
3. Hyposalivation was comparable in both drugs.
4. The NANC innervation of the mini pig is about 10 to 15%.

propiverine hydrochloride                                             tolterodine

median               37               17                4                                  47                14                 6

Tab: Results of the stimulation-induced bladder pressure just before and 40 minutes after administration of propiverine hydrochloride (No. 1 to 5) and tolterodine (No. 6-10) as well as after administration of atropine at the end of the trial.